title: Nifedipine enhances cholesterol efflux in RAW264.7 macrophages.
abstract: OBJECTIVE
  Studies have shown that nifedipine protects against atherosclerotic progression, but its underlying mechanisms remain unclear. In this study, we examined if nifedipine increases macrophage cholesterol efflux, a pathway known to inhibit atherogenesis.
  
  
  METHODS
  We evaluated the ability of different doses of nifedipine to affect cholesterol efflux in RAW264.7 macrophages and its relationship with mRNA and protein levels of several well-characterized proteins involved in cholesterol efflux, including ABCA1, ABCG1, SR-BI and LXRα, using quantitative real-time PCR, Western blotting, and siRNA techniques.
  
  
  RESULTS
  Nifedipne at 1, 10, and 100 nmol/L increased apoA-I-mediated cholesterol efflux from 2.55 % to 5.65 %, 6.20 %, and 6.10 %, as well as HDL-mediated cholesterol efflux from 31.0 % to 42.5 %, 46.0 %, and 43.5 %, respectively, in RAW264.7 macrophages (p < 0.05), which was associated with increased mRNA expression levels of ABCA1, ABCG1, SR-BI, and LXRα (405 %, 381 %, 336 %; 890 %, 960 %, 1002 %; 285 %, 325 %, 336 %; 482 %, 445 %, 405 %, respectively, p < 0.05), and with increased protein levels of ABCA1, ABCG1, SR-BI, and LXRα (428 %, 492 %, 361 %; 288 %, 331 %, 365 %; 283 %, 320 %, 505 %; 581 %, 678 %, 608 %, respectively, p < 0.05). SiRNA-mediated silencing of LXRα revealed that LXRα was involved in these increases and the enhanced cholesterol efflux.
  
  
  CONCLUSIONS
  Nifedipine may protect against atherosclerosis partly by promoting macrophage cholesterol efflux through the stimulation of LXRα-dependent expression of ABCA1, ABCG1, and SR-BI.
authors.affiliation: Department of Cardiology, Southwest Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: A Zhi Sha
authors.initials: AZ
authors.lastname: Ma
authors.forename: Zhi Yuan
authors.initials: ZY
authors.lastname: Song
authors.forename: Chan
authors.initials: C
authors.lastname: Wang
authors.forename: Xiao Dan
authors.initials: XD
authors.lastname: Fu
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology*; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D002121:Calcium Channel Blockers; D002784:Cholesterol; D008074:Lipoproteins; D000071518:Liver X Receptors; D009543:Nifedipine; D057093:Orphan Nuclear Receptors; D051122:Scavenger Receptors, Class B; C577833:Abca1 protein, mouse; C487540:ABCG1 protein, mouse; C000605214:Nr1h3 protein, mouse; C454739:Scarb1 protein, mouse